Ataxia telangiectasia (AT), Louis-Bar syndrome, is a rare neurodegenerative disorder caused by autosomal recessive biallelic mutations within the ataxia telangiectasia mutated (ATM) gene. Currently, there are no curative therapies available for this disorder. This review provides an overview of the latest advances in treatment methods including 1- Acetyl-DL-leucine, 2- Bone Marrow Transplantation, 3- Gene Therapy, 4- Dexamethasone, and finally 5- Red Blood Cells (RBCs) as a carrier for dexamethasone (encapsulation of dexamethasone sodium phosphate into autologous erythrocytes, known as EryDex). Most of the treatments under investigation are in the early stages, except for the EryDex System. It appears that the EryDex system and N-Acetyl-DL-Leucine may hold promise as potential treatment options.

Genomic instability disorders are characterized by DNA or chromosomal instability, resulting in various clinical manifestations, including developmental anomalies, immunodeficiency, and increased risk of developing cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article discusses childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anticancer therapy.

Ataxiatelangiectasia (A-T) is an infrequent genetic neurodegenerative disorder inherited autosomal recessively. It is mainly characterized by early-onset progressive cerebellar ataxia and dilated capillaries in the oculocutaneous regions especially conjunctivae so-called telangiectasia. A-T is a multisystem disorder and requires multi-disciplinary approach to management. Diagnosis is difficult in some cases because presentation is not in the same manner and showing a phenotypic spectrum. In atypical cases serum immunoglobulins and alfa fetoprotein are normal and telangiectasia is absent. We present a 5.5-year-old boy with progressive cerebellar ataxia and history of repeated sino-pulmonary infections that was homozygote for ataxia-telangiectasia mutated gene and had a giant arachnoid cyst in left hemisphere. It is important to keep in mind those cases with ataxia and repeated sino-pulmonary infections may be ataxia telangectasia patients. Genetic study is helpful and confirms the diagnosis by showing ataxia-telangiectasia mutated gene.

Hereditary ataxia (HA) is a diverse group of rare inherited neurological disorders characterised by cerebellar impairment and the progressive degeneration of spinocerebellar tracts and the spinal cord. These conditions manifest predominantly as unsteady gait, speech difficulties, dysphagia and motor skill impairment. The complex genetic causes and varied disease mechanisms underlying HA contribute to the multi-systemic symptoms which pose challenges in developing targeted effective treatments. Currently, available options for HA primarily focus on symptomatic management, highlighting a critical need for complementary therapeutic strategies, such as dietary and lifestyle interventions. This review explains recent findings on dietary and nutraceutical interventions, as well as lifestyle modifications such as exercise and rehabilitation programs for HA. It outlines common types of HA, including Friedreich ataxia, spinocerebellar ataxias, ataxia with vitamin E deficiency, ataxia-telangiectasia, and studies on a mixed cohort of patients with HA. The current management options, therapeutic implications of findings from pre-clinical and clinical data and future directions to advance the treatment of HA will also be discussed. The integration of nutraceuticals and rehabilitation programs with current methods of symptomatic management is encouraged for the holistic treatment of HA. These interventions will complement the use of various technological aids with the support of a multidisciplinary health and medical team to improve monitoring of the health status and disease progression of affected individuals; thus facilitating early treatment and an optimised clinical outcome.

Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene, predisposing children to hematological malignancies. We investigated their characteristics and outcomes to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries. Ninety-one patients (45%) presented with mature B-cell lymphomas, 82 (41%) with acute lymphoblastic leukemia/lymphoma, 21 (10%) with Hodgkin lymphoma and 8 (4%) with other hematological malignancies. Four-year overall survival and event-free survival (EFS) were 50.8% (95% confidence interval [CI], 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively. Cure rates have not significantly improved over the last four decades (P = .76). The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI, 19.5-32.4). Germ line ATM PVs were categorized as null or hypomorphic and patients with available genetic data (n = 110) were classified as having absent (n = 81) or residual (n = 29) ATM kinase activity. Four-year EFS was 39.4% (95% CI, 29-53.3) vs 78.7% (95% CI, 63.7-97.2), (P < .001), and TRM rates were 37.6% (95% CI, 26.4-48.7) vs 4.0% (95% CI, 0-11.8), (P = .017), for those with absent and residual ATM kinase activity, respectively. Absence of ATM kinase activity was independently associated with decreased EFS (HR = 0.362, 95% CI, 0.16-0.82; P = .009) and increased TRM (hazard ratio [HR] = 14.11, 95% CI, 1.36-146.31; P = .029). Patients with A-T and leukemia/lymphoma may benefit from deescalated therapy for patients with absent ATM kinase activity and near-standard therapy regimens for those with residual kinase activity.

Background: Ataxia telangiectasia (A-T) is a DNA repair disorder with cancer predisposition.

Objective: We sought to characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T.

Methods: Data were retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios of cancer, survival probability after cancer diagnosis, and standardized mortality ratios were calculated. Cox regression estimated risk of death on the basis of chemotherapy (standard vs reduced) dosing, and multivariable logistic regression evaluated cancer risk associations with ataxia telangiectasia mutated (ATM) exons and variants.

Results: Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, of whom 62 (74%) were hematologic in origin and 22 (26%) were solid-organ cancers. The cumulative incidence of cancer was 29% by age 35 years. Non-Hodgkin lymphoma occurred most frequently (n = 39), whereas solid cancers disproportionately affected those 18 years and older (n = 22). The standardized mortality ratio was 24.6 (95% CI, 21.1-28.4) overall and 232.9 (95% CI,178.1-299.2) among individuals with cancer. Risk of death was higher when treated with standard/unknown versus modified chemotherapy (hazard ratio, 2.2; 95% CI, 1.1-4.4; P = .024). Chemotherapy-associated toxicities developed in 58% of individuals, predominantly neurologic (n = 14) and gastrointestinal (n = 10) systems. Three exons were enriched for cancer-associated variants.

Conclusions: Individuals with A-T experience a wide array of blood and solid-organ malignancies, high mortality rates, and treatment-related toxicities, highlighting need for targeted therapies to mitigate toxicity and optimize survival.